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GERIATRIC THERAPY

GERIATRIC THERAPY. Marian G. Suarez, M.D. Diplomate, American Board of Internal Medicine and Geriatrics. The world population is aging. Data from US Bureau of Census showing some projected population growth number. The Pharmacology of Aging.

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GERIATRIC THERAPY

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  1. GERIATRIC THERAPY Marian G. Suarez, M.D. Diplomate, American Board of Internal Medicine and Geriatrics

  2. The world population is aging. Data from US Bureau of Census showing some projected population growth number. The Pharmacology of Aging

  3. World Demographics(US Bureau of Census, International Database, 1996)Merck Manual,Geriatrics,1999 1. Growth of 65+ • increase dramatically 1996-2025 • % of ≥60 years old expected to increase from 17% to 82% in Europe (about 200% in developing countries) 2. China and India • Has the largest total population • Will have the largest absolute numbers of elderly

  4. World Demographics(US Bureau of Census, International database, 1996)Merck Manual,Geriatrics,1999 • 2020: Expected to have >1 billion persons ≥60 yrs old • 85 yrs old and over: “Oldest old” will increase to 18 million by 2050 • Centenarians will increase from 57,000 persons (1996) to 447,000 (2040)

  5. Epidemiology of Medication Use in the Elderly • 65 + comprise 13% US population consume 30% of all prescription drugs consume 40% of all non-prescription drugs 2. 2004: Health care cost for >65 + ~50% of National Health Care Bill (substantial portion spent on medications)

  6. Epidemiology of MedicationUse in the Elderly 3. On average-older adult uses 2-4 different prescription drugs at the same time 4. Community dwellers (65-84) – 61% >3 drugs/year 37% receive ≥ 5 19% receive >7 5. Elderly NH patient- receive 6-8 meds daily 33%- 9-14 drugs daily

  7. Epidemiology of Medication Use in the Elderly 6. Women more likely than men • use prescription medication 7. Several studies show at least 90% of elderly use 1 + over the counter drugs (OTC) 8. Most common OTC drugs: Analgesics,Vitamins,Nutritional supplements,Laxatives, Antacids,Antihistamines

  8. Epidemiology of Medication Use in the Elderly 9. Polypharmacy associated with increase incidence of adverse drug reactions (ADRs) 10. ADR responsible for 10-17% of hospital admissions of elderly outpatients (other studies: ADR→35% of all hospital admission in the high risk elderly ≥ 5 drugs daily

  9. Prevention Rapid identification And resolution of drug-related problems Major Responsibility of the Pharmacist

  10. Categories of Drug-Related Problems • Untreated medical problem (patient with medication problem require prescription drug but does not receive the drug) • Improper drug selection (taking the wrong drug) • Underdosage (too little of correct drug) • Failure to receive drug

  11. Categories of Drug-Related Problems 5. Overdosage 6. Adverse Drug Reaction 7. Drug Interaction (drug-drug ;drug-food; drug-disease interaction) 8. Drug use with no indication

  12. WHO Definition of ADR (Adverse Drug Interaction) • Noxious, unintended & undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis or therapy • Excludes: • therapeutic failures • intentional/ accidental overdoses • drug abuse • “adverse events” due to error in drug administration or noncompliance

  13. History of ADR • 1960-1970’s – data suggested age as a risk factor for development of ADR • 1980 – spontaneous ADR reports to FDA indicating rate of ADR in 65+ y/o, nearly double of younger individuals (problem of inappropriate Rx to older individuals was acknowledged & publicized by medical & advocacy groups for this elderly

  14. History of ADR • 1980-1990 – gov’t regulatory & legislative occurred to improve policy making; and to decrease ADR in geriatric patients • 1987 – Omnibus Budget Reconciliation Act (OBRA) established regulations for use of sedative-hypnotics & antipsychotics in Medicare-certified NH

  15. History of ADR (continued…) • 1990 – OBRA required all states to conduct DUR (Daily Utilization Reviews) of Medicaid Rx drug claims • 1995 – Report on “Prescription Drugs and the Elderly” concluded inappropriate use of Rx drugs = significant health problems in the elderly • 2001 – FDA released a guidance for industry to submit revised labeling for drugs already in the market

  16. Prescribers, Dispensers and Monitors of medication must understand age-related changes affecting the dispositon of drugs.

  17. Age-Related Changes in Pharmacokinetics Pharmacokinetics • study of the absorption, distribution, metabolism, and excretion of drug • “what the body does to the drug” Pharmacodynamics • “what the drug does to the body”

  18. Drug Administration (route: oral, intravenous, intravascular, inhalational, intranasal, topical) Schematic Representation of Drug Pathway Absorption Bioavailability (ie. Fraction of drug available- variable) Metabolism (liver, kidney, others) Distribution Depot drug: Circulating drug: Lipid Protein-bound Water Free Excretion Drug Effect Renal (glomerular filtration, tubular secretion) Benefit (efficacy) Adverse Effect (side effect or toxicity) Hepatic Other (skin, lung, gastrointestinal)

  19. Drug Absorption Age-related physiologic changes can include: Decreased acid production Decreased absorptive surface (mucosal atrophy) Decreased splanchnic perfusion Decreased GI motility Generally no significant age-related ABSORPTION for most drugs Pharmacokinetic Principles in the Elderly

  20. BIOAVAILABILITY • BIOAVAILABILITY – refers to the fraction of an administered drug that reaches the circulation - variable • IV med – 100% • Oral drug usually later

  21. Pharmacokinetic Principlesin the Elderly • Drug distribution • Age-related physiologic changes include: • Decreased total body water- water-soluble drugs (lithium, digoxin, aminoglycosides: lower maintenance dose to avoid ADR) • Decreased lean body mass • Decreased serum albumin (binds acid i,e.warfarin, phenytoin)

  22. Pharmacokinetic Principlesin the Elderly • Increased a1- acid glycoprotein (AAG)- binds basic drugs (lidocaine, propranolol) • Protein-bound [inactive drug] • Free drug [active drug] ie. Warfarin 99% protein-bound, has increased anticoagulant activity & toxicity in patients w/ decreased albumin levels • Increased total body fat • Lipid-soluble drugs (eg benzodiazepines) increase volume of distribution in elderly; remain in fat depots for prolonged period exerting their effect long after drug has been withdrawn

  23. Pharmacokinetic Principlesin the Elderly • Drug Metabolism • Age-related physiologic changes include: • Decreased hepatic mass • Decreased hepatic blood flow (40%) • Age-related decrease in liver blood flow directly influence the rate of drug extraction from the blood

  24. Pharmacokinetic Principlesin the Elderly • Drugs are metabolized in the liver by Phase I or Phase II metabolism • Phase I metabolism (e.g. oxidation, reduction, hydrolysis) declines in the elderly due to decreased hepatic blood flow ( to nearly half by 85y/o) • Diazepam/ Flurazepam w/ prolonged duration of activity • Phase II metabolism- primarily conjugation (e.g. glucoronidation, sulfation) less affected by aging

  25. Pharmacokinetic Principlesin the Elderly • Cytochrome P450 (CYP) system- family of enzymes involved in oxidative metabolism • Comprises 3 major groups: • CYP1 • CYP 2 • CYP 3A – accounts for metabolism of ~ 50% of drugs • CYP minimally altered by age alone • Many drugs/ other substances alter effects of CYP enzymes • Multiple drugs may induce or inhibit CYP450 enzymes

  26. Common Inhibitors & Inducers of CP 450 Enzymes

  27. Pharmacokinetic Principlesin the Elderly • Drug excretion • Age-related physiologic changes include: • Decreased renal blood flow ( creatinine clearance) • Decreased GFR (~ 50% bet. ages 20-90) – “unbound drugs” • Decreased tubular secretion (protein bound drugs)

  28. Pharmacokinetic Principlesin the Elderly • Drugs potentially toxic in the elderly due to predominant renal elimination: • Aminoglycosides, amantadine, lithium, digoxin, procainamide, cimetidine, NSAIDS

  29. Pharmacokinetic Principlesin the Elderly • Glomerular Filtration Rate (GFR) is approximated by calculating creatinine clearance. The formula, Cockroft & Gault Equation, is used to adjust drug dosage: • Creatinine clearance= 140-age x wt (kg) 72 x serum creatinine • In females, the result is multiplied by 0.85

  30. Age-related Changes in Pharmacodynamics • “what drug does to the body”- may be due to changes in: • Drug receptors- blunted homeostatic mechanism predisposes to respiratory depression, sedation & constipation • Drug-receptor interaction- less active baroreceptor reflexes predispose elderly on antihypertensives to postural hypotension • Altered adaptive homeostatic responses or organopathology- impaired thermoregulatory response to cooling predispose them on barbiturates or phenothiazines in hypothermia

  31. Primary Approaches to Determine Appropriateness of medication Prescribing in the Elderly • Drug Lists- most familiar “BEERS CRITERIA” • Published 1991- identified inappropriate meds use in NH residents • (19 meds to be avoided, 11 criteria re: doses, frequencies, duration of med Rx that should not be exceeded in frail NH residents) • Updated 1997- to apply to older people in all care settings • (28 medications to be avoided, doses & frequencies of administration not to be exceeded & 35 meds to be avoided in elderly known to have any of several common conditions (drug-disease criteria)

  32. Drug Utilization Review (DUR) • Evaluation of drug use in a given health environment against predetermined criteria to assess appropriateness of drug therapy • Implicit Method • Focus on appropriateness of a patients’ entire medication regimen rather than on a single drug or drug class & combines medical history and the clinician’s judgment & knowledge

  33. 6 Domains to Measure Inappropriate Prescribing • Lack of indication • Improper schedule • Inadequate dosage • Potential drug interaction • Therapeutic duplication • Allergy

  34. Suboptimal Prescribing • Overuse or Polypharmacy • Prescribing w/o proper indication • According to patient expectation for a prescription • Polypharmacy can lead to ADRs • Contributes to development of several “geriatric syndromes” ie. cognitive impairment, delirium, falls, urinary incontinence & increases health care costs • Inappropriate Use • Rx of a med w/ more potential risk than benefit • Rx that does not agree w/ accepted medicine standards • Improper drug selection • Appropriate drug but wrong dose (too low/too high)

  35. Suboptimal Prescribing • Underutilization • Omission of a drug indicated for Rx or prevention of a disease condition • Underprescribing [ie. Use of warfarin for atrial fibrillation; Rx of cancer pain]

  36. Appropriate Rx for the Elderly • Dosage determination • “start slow & go slow” • Compliance • Unintentional noncompliance- due to forgetfulness, confusion, decreased vision • Intentional noncompliance- due to side effects; financial barriers • Role of Pharmacist • Provide services in DUR • Improve compliance • Simplify drug regimens • Increase patient education

  37. General Principles for Improved Geriatric Prescribing • Obtain thorough history of a drug use from all physicians & sources • Evaluate the need for drug therapy • Periodically review medication regimen/ avoid polypharmacy • Know pharmacology of drug(s) prescribed • Check renal function & adjust drug doses accordingly • Simplify drug regimen/ help ensure compliance • Develop awareness of the COST of medications

  38. 1997 Beers criteria

  39. Comparisons of Initial Doses Recommended in FDA- approved Product labeling versusLower Effective Doses Reported in the Medical Literature

  40. Comparisons of Initial Doses Recommended in FDA- approved Product labeling versusLower Effective Doses Reported in the Medical Literature

  41. Comparisons of Initial Doses Recommended in FDA- approved Product labeling versusLower Effective Doses Reported in the Medical Literature

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